The aim of the review was to examine the effectiveness of misoprostol as co-therapy in the prevention of non-steroidal anti-inflammatory drug-induced gastrointestinal mucosal injury. The outcomes assessed were the number of patients in whom a gastric ulcer developed, the number of patients in whom gastric lesions developed, the number of patients in whom a duodenal ulcer developed and the number of patients in whom duodenal lesions developed. The weighted average baseline risks for gastric ulcers were found to be 3.8% and 6.8% with short- and long-term non-steroidal anti-inflammatory drug treatment, respectively. Misoprostol treatment resulted in a significant (p<0.05) risk reduction of gastric ulcer in the short-term (pooled RD=13.3%; 95% confidence interval -25.7%, -0.9%) and in the long-tenn (RD=-8.4%; 95% confidence interval -17.7%, -1.0%) nonsteroidal anti-inflammatory drug treatment The weighted average baseline risks for duodenal ulcers were found to be 3% and 4% with short- and long-term non-steroidal anti-inflammatory drug treatment respectively. Misoprostol did not significantly reduce the risk of duodenal ulcers with short treatment (RD=-2.0%; 95% confidence interval -5.7%, 1.6%). Treatment was effective in the long-term nonsteroidal anti-inflammatory drugs therapy (RD=3.4%; 95% confidence interval -5.8%, -0.1%, p<0.001). The number of patients needed to be treated to prevent 1 person from developing a gastric ulcer within 2 weeks of non-steroidal anti-inflammatory drug therapy was found to range from 35, when baseline risk was 3%, to 3 when the baseline risk was higher say 40%. The corresponding number of patients needed to be treated for gastric ulcer prevention in long-term studies ranged from 47 To 5. The number of patients needed to be treated for prevention of duodenal nicer with misoprostol in short-term studies ranged from 36 to 4 and in the long-term trials form 47 to 8. In conclusion, a rational approach to treat only high risk patients is recommended.